Kynurenic acid, a key L-tryptophan-derived metabolite, protects the heart from an ischemic damage

Einat Bigelman, Metsada Pasmanik-Chor, Bareket Dassa, Maxim Itkin, Sergey Malitsky, Orly Dorot, Edward Pichinuk, Yuval Kleinberg, Gad Keren, Michal Entin-Meer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background Renal injury induces major changes in plasma and cardiac metabolites. Using a small- animal in vivo model, we sought to identify a key metabolite whose levels are significantly modified following an acute kidney injury (AKI) and to analyze whether this agent could offer cardiac protection once an ischemic event has occurred. Methods and results Metabolomics profiling of cardiac lysates and plasma samples derived from rats that underwent AKI 1 or 7 days earlier by 5/6 nephrectomy versus sham-operated controls was performed. We detected 26 differential metabolites in both heart and plasma samples at the two selected time points, relative to sham. Out of which, kynurenic acid (kynurenate, KYNA) seemed most relevant. Interestingly, KYNA given at 10 mM concentration significantly rescued the viability of H9C2 cardiac myoblast cells grown under anoxic conditions and largely increased their mitochondrial content and activity as determined by flow cytometry and cell staining with MitoTracker dyes. Moreover, KYNA diluted in the drinking water of animals induced with an acute myocardial infarction, highly enhanced their cardiac recovery according to echocardiography and histopathology. Conclusion KYNA may represent a key metabolite absorbed by the heart following AKI as part of a compensatory mechanism aiming at preserving the cardiac function. KYNA preserves the in vitro myocyte viability following exposure to anoxia in a mechanism that is mediated, at least in part, by protection of the cardiac mitochondria. A short-term administration of KYNA may be highly beneficial in the treatment of the acute phase of kidney disease in order to attenuate progression to reno-cardiac syndrom and to reduce the ischemic myocardial damage following an ischemic event.

Original languageEnglish
Article numbere0275550
JournalPLoS ONE
Issue number8 August
StatePublished - Aug 2023


Dive into the research topics of 'Kynurenic acid, a key L-tryptophan-derived metabolite, protects the heart from an ischemic damage'. Together they form a unique fingerprint.

Cite this